Craig R W, Sager R
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2062-6. doi: 10.1073/pnas.82.7.2062.
Somatic cell hybridization experiments were carried out to determine whether normal cells have the ability to suppress the transforming effects of a defined oncogene. A nontransformed Chinese hamster embryo fibroblast cell line (CHEF/18-dm2) was used as the normal parent, and a CHEF/18 transfectant carrying the human mutant c-Ha-ras (EJ) oncogene was used as the tumorigenic parent. Selected hybrids (L318 cell lines) were assayed for the presence of EJ DNA, for the p21 product of the c-Ha-ras gene, and for various indices of cell transformation. These hybrids exhibited a fibroblastic morphology similar to the normal parent, although they contained the EJ gene and expressed its p21 protein product at levels comparable with the transformed parent. They had a reduced capacity for anchorage-independent growth (plating efficiency in methylcellulose of less than 0.3-13%, as compared with greater than 90% for the transformed parent) and decreased tumor-forming ability in athymic mice. These findings show that normal CHEF/18 cells contain suppressor genes capable of inhibiting expression of the transformed phenotype, and tumor-forming ability, in the presence of an activated EJ oncogene.
进行了体细胞杂交实验，以确定正常细胞是否具有抑制特定癌基因转化作用的能力。一种未转化的中国仓鼠胚胎成纤维细胞系（CHEF/18-dm2）用作正常亲本，一种携带人突变型c-Ha-ras（EJ）癌基因的CHEF/18转染细胞用作致瘤亲本。对选定的杂种细胞（L318细胞系）进行检测，以确定其是否存在EJ DNA、c-Ha-ras基因的p21产物以及各种细胞转化指标。这些杂种细胞呈现出与正常亲本相似的成纤维细胞形态，尽管它们含有EJ基因并表达其p21蛋白产物，表达水平与转化亲本相当。它们在非贴壁生长方面的能力降低（在甲基纤维素中的接种效率低于0.3 - 13%，而转化亲本则大于90%），并且在无胸腺小鼠中的致瘤能力下降。这些发现表明，在存在激活的EJ癌基因的情况下，正常的CHEF/18细胞含有能够抑制转化表型表达和致瘤能力的抑制基因。
